dr. Indriati Dwi Rahayu

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PENDAHULUAN

SEL-SEL

HEMATOPOIESIS

(3)

Umum

- Special connective tissue

• Total volume: + 5 L, + 8 % body weight • Composition :

√ plasma : tersebar unsur padat, protein, hormon

√ unsur padat : blood cells

STAINING : Wright, Giemsa, Romanowsky,

(4)

Composition of PLASMA

Formed elements : blood cells

(5)

PENDAHULUAN

SEL-SEL DARAH

HEMATOPOIESIS

(6)

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L E U C O C Y T E S

sel2 DARAH

HARGA NORMAL FUNGSI STRUKTUR KORELASI KLINIS

!

(7)

KOMPONEN PADAT  45 %

1. Red Blood Cell = Erythrocyte

- Normal value: 4 - 6 X 106 /μL

- Life span : 120 hr  lien dan sum2 tulang

- hematocrit : perkiraan volume eritrosit per unit volume darah. Harga normal : laki2 :40–50% ; wanita : 35–45%

(8)

- FUNGSI :

* untuk transpor O2 (oleh Hemoglobin) * buffer asam-basa (oleh Hemoglobin)

* katalisator reaksi ( dg enzym karbonik anhidrase)

HEMOGLOBIN

* Tdd 4 polipeptida, @ memiliki 1 Heme * Type (berdasar asam amino)

1. Hb A1 : 97 % 2. Hb A2 : 2 %

3. Hb F : 1 %. (pada neonatus 80%)

4. Hb S : abnormal dr Hb A  Sickle cell anemia

(9)

- STRUKTUR :

* Ф : 7 – 8 μm, (sediaan segar lebih besar; warna kuning kehijauan)

* bikonkaf ; bag tengah: central pallor * (matur) : inti dan organella (-)

* Sitoplasma Isotonis; mengandung Hb

* Plasmalemma : tdd membran protein integral: Dalam  Spectrin

Luar  Mengandung antigen * Bersifat fleksibel

* Cenderung saling melekat  Rouleaux formation (hanya sementara)

(10)

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- abnormalitas struktur:

* Anisositosis : RBC dalam ukuran bervariasi * Poikilositosis : RBC bentuknya bervariasi * Makrositer : Ø > 9 µm

* Mikrositer : Ø < 6 µm

* Cabot ring = Howell Jolly body : fragmen inti. (> 1 %) Pengecatan : Brilliant Cresyl Blue utk melihat sisa

RER & ribosom pada retikulosit * Crenated : mengkerut. Karena suasana hipertonis * Spherocytosis : Spheroidal erythrocyte

(12)

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KLINIS

• Keluhan yg relevan : pucat • Anemia : Hb ↓

– may be caused by :

 loss of blood (hemorrhage);

 insufficient production of RBC by the bone marrow;

 production of RBCs with insufficient hemoglobin, usually related to iron deficiency in the diet; or

 accelerated destruction of blood cells.

– Ex : Sickle cell anemia : The sickled erythrocyte is inflexible & fragile  shortened life span that leads to anemia.

It increases the blood viscosity and can damage the walls of blood vessels, promoting blood coagulation. Blood flow

through the capillaries is retarded or even stopped, leading to severe O2 shortage (anoxia) in tissues.

(15)

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L E U C O C Y T E S

sel2 DARAH

(16)

2. LEKOSIT - jumlah normal: 6000 – 10.000 / μL - dasar klasifikasi : ~ diameter ~ Bentuk inti ~ Ratio inti-sitoplasma ~ Pengecatan

(17)

• Karakteristik umum :

- sel sejati  inti & organella [+] - gerak amuboid & diapedesis [+]

- berfungsi di jaringan ikat. Aliran darah hanya sebagai sarana transportasi

- pada sediaan permanen ukuran lebih besar - granul azurophilic, with lytic enzymes

• klasifikasi dengan pengecatan khusus  diff.count (hitung jenis)

(18)

- Granulosit,

* = PMN (polymorpho nuclear)

* organella: [matur] Inti berlobus, Golgi,mitokondria, free ribosom,RER

* specific granules dan azurophilic granules; * TERDIRI DARI : Eosinofil, Basofil, dan Netrofil

- Agranulosit

* mononuclear ; unsegmented * granul azurophilic ONLY

* TERDIRI DARI : Limfosit, Monosit

(19)

Keluhan yang relevan :

- Infeksi

- Keganasan

(20)

Leukocytosis

• An increase in the number of circulating leukocytes occurs as a normal protective reaction in a variety of pathological conditions, especially in response to infections.

• Pathological leukocytosis : leukocyte count more than 11 x 109_{/1 (11. 000/mm3)}

• Drug involved : ex : corticosteroid, litium

Leukopenia

the total blood leukocyte count : less than 4 x 109_{/1 (4000/mm3)}

Drug involved : ex : Minocycline, clozapine .

(21)

Granulocytopenia (neutropenia)

This is a general term used to indicate an abnormal

reduction in the numbers of circulating granulocytes

(polymorphonuclear leukocytes), commonly called

neutropenia because 40 to 75% of granulocytes are

neutrophils. A reduction in the number of circulating

granulocytes occurs when production does not keep

pace with the normal removal of cells

(22)

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L E U C O C Y T E S

sel2 DARAH

(23)

• Eosinofil :

- % WBC : 1-4 % - Karakteristik :

* >> di sirkulasi saat reaksi alergi & infeksi parasit * gerak diapedesis [+]

* kemampuan fagositosis terbatas, t.u kompleks Ag-Ab

* responsif dengan pemberian steroid ( = Thorn test)

(24)

STRUKTUR :

• Φ : (sirkulasi) : 9 µm (jaringan) : 14 µm - Sitoplasma :

* granul lebih besar, refraktil, uniform

* granul mengandung lisozym khusus (peroxidase, acid fosfatase, cathepsin, ribonuclease, Eosinophilic

antiparasitic agent) + azurophilic • Inti :

- chromatin padat

(25)

- Peran : * respon thd infeksi parasit * modulasi proses inflamasi

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KLINIS :

Eosinophilia : associated with allergic reactions and helminthic (parasitic) infections.

Corticosteroids can produce a rapid decrease in the number of blood eosinophils, probably by interfering with their release from the bone marrow into the bloodstream

(28)

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L E U C O C Y T E S

sel2 DARAH

(29)

• Basofil :

- % WBC : 0-1 % - karakteristik :

* mirip mast cell, kecuali ultrastrukturnya

* kemampuan gerak amuboid & fagositosis terbatas

- Peran :

 dalam reaksi immediate hipersensitivity;  menghasilkan mediator radang

(30)

- Struktur :

* Φ :10-12 µm (lbh kecil dr netrofil) * Sitoplasma :

- kurang padat

- ukuran granul bervariasi, granul spesifik gelap - Granul mengandung heparin, histamin

* Inti :

chromatin padat, lebih pucat

(31)

KLINIS

cutaneus basophil hypersensitivity : penumpukan extravaskular karena inflamasi

(32)

RBC

EOSINOPHYL

BASOPHYL

NETROPHYL

LYMPHOCYTE

MONOCYTE

THROMBOCYTE

L E U C O C Y T E S

sel2 DARAH

(33)

Netrofil :

- dominan, 60-70 % - tidak dapat mitosis

(34)

- karakteristik :

> gerak amuboid  keluar pembuluh darah  ~ makrofag aktif = microphage

> kemampuan mitosis [-]

> 2 macam granule ( specific & azurophilic) > klasifikasi (menurut Schiling) :

~ Netrofil segmented (57 %)

Meningkat : shift to the right - Netrofil nonsegmented (stab) (4%) Meningkat : shift to the left

(35)

STRUKTUR

• Φ : (sirkulasi) : 12 µm (jaringan) : 20 µm • Sitoplasma :

- warna : salmon-pink

- Granul spesifik : Alkaline phosphatase, lysozym, Laktoferin kolagenase, protein antibacterial

non-enzimatik (ex; Phagocytin)

- Granul Azurofilik : Acid phosphatase, myeloperoxidase, protein antibakterial kationik, dll

(36)

Inti : • chromatin padat • multilobus • macam : * hipersegmented ( >5 )  tua * segmented * stab

• [wanita] drumstick=Barr body, mrpkn kromosom X inaktif (menempel pada inti)

(37)

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KLINIS :

An increased number of band neutrophils in the blood

indicates a higher production of neutrophils, probably in response to a bacterial infection.

( Immature neutrophils that have recently entered the blood circulation have a nonsegmented nucleus in the shape of a horseshoe (band forms))

(39)

RBC

EOSINOFIL

BASOFIL

NETROFIL

LIMFOSIT

MONOSIT

TROMBOSIT

(40)

Limfosit :

 % wbc :20 – 25 %

 di luar pembuluh darah : organ limfatik & jaringan

ikat

 Dapat berRESIRKULASI

 terbagi dalam 2 kelas : limfosit T (most) & B  Peran : sesuai jenis sel.

sel T : berperan dalam immunitas seluler sel B : berperan dalam immunitas humoral;

berdiferensiasi menjadi Sel Plasma;  menghasilkan Imunoglobulin

 ! TIDAK DAPAT FAGOSITOSIS

(41)

 Struktur :

* Φ: Kecil 6 – 8 µm

Med-besar :8-18 µm * Sitoplasma :

[kecil] :dekat inti tipis, basofil pucat, warna biru kehijauan

>> ribosom; Organella lain << (tidak khas) [med-besar] : lebih banyak, (lain sama)

(42)



Inti :

[kecil] : - Bulat / pipih, dengan indentasi 1 sisi - heterochromatis padat

- warna : biru s/d hitam- keunguan [med-besar] : lebih besar

kurang heterocromatis

(43)

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CLINICAL CORRELATION

AIDS

• HIV-infected adolescents and adults categorizes

persons on the basis of clinical conditions associated with HIV infection and CD4+ T lymphocyte counts

SEVERE COMBINED IMMUNODEFICIENCY

• The SCID syndrome is characterized by gross functional impairment of both humoral and cell-mediated immunity and by susceptibility to devastating fungal, bacterial,

(45)

RBC

EOSINOFIL

BASOFIL

NETROFIL

LIMFOSIT

MONOSIT

TROMBOSIT

(46)

Monosit (large mononuclear leucocyte) : - % WBC : 3 – 8 %

- Karakteristik :

hanya di darah

Di luar sirkulasi  fagositosis kemampuan resirkulasi [-]

gerak pseudopodia seperti octopus, dg inti di depan - Peran :

• Generation of mononuclear-phagocyte system cells in tissues;

• phagocytosis and digestion of protozoa and virus and senescent cells

(47)

The monocyte-macrophage system consists of the body's complement of monocytes and macrophages. Some macrophages are mobile whereas others are fixed. These include:

• histiocytes in connective tissues • microglia in the brain

• Kupffer cells in the liver

• alveolar macrophages in the lungs

• sinus-lining macrophages (reticular cells) in the spleen, lymph nodes and thymus gland

• mesangial cells in the glomerulus of nephrons in the kidney

(48)

Struktur :

- Φ: (sirkulasi) : 12-15 µm (jaringan) : 20 µm -Sitoplasma : * warna biru keabu-abuan

* >> granul azurofilik

* >> mitokondria & golgi & RER * Ribosom bebas <<

- Inti : * p.u bentuk ginjal, eksentris

* lebih pucat (kromatin lebih halus) * 2-3 nucleoli

(49)

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CLINICAL CORRELATION

• Monocytopenia occurs with acute infections, with stress, and after treatment with glucocorticoids. Monocytopenia also occurs in aplastic anemia, hairy cell leukemia, acute myeloid leukemia, and as a direct result of myelotoxic drugs.

• Monocytosis is associated with tuberculosis, brucellosis, subacute bacterial endocarditis, Rocky Mountain spotted fever, malaria, and visceral leishmaniasis (kala azar).

Monocytosis also occurs with malignancies, leukemias, myeloproliferative syndromes, hemolytic anemias, chronic idiopathic neutropenias, and granulomatous diseases such as sarcoidosis, regional enteritis, and some collagen vascular diseases.

(51)

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RBC

EOSINOFIL

BASOFIL

NETROFIL

LIMFOSIT

MONOSIT

TROMBOSIT

(53)

PLATELET (thrombocyte=thromboplastid)

- berasal dr ―budding’ megakariosit di sumsum tulang - Σ Normal : 200.000-400.000/Μl, lifespan : 8 hari

- Fungsi : CLOT FORMATION

• Primary aggregation—Discontinuities in the

endothelium,  platelet aggregation  platelet plug • Secondary aggregation—Platelets in the plug

release an adhesive glycoprotein and ADP.  increasing the size of the platelet plug.

• Blood coagulation -- cascade, giving rise to a polymer, fibrin  thrombus.

(54)

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- Struktur :

 Ø : 2-5 μm; dalam sediaan nampak berkelompok  Bentuk seperti cakram, biconvex

 pd sediaan segar : tidak berwarna

 permukaan membran : Glycocalyx untuk adhesi  tepi : hyalomere,warna biru pucat. Terdapat

marginal bundle

 central : dense granulomere, Terdapat mitokhondria, granul glikogen, dan granul2 warna ungu. Jenis granul : δ, α, λ

(56)

(57)

CLINICAL CORRELATION

THROMBOCYTOPENIA

This is defined as a blood platelet count below 150 x 109_/1

(150 000/mm3) but spontaneous capillary bleeding does not usually occur unless the count falls below 30 x 109_/1

(30 000/mm3).

Thrombocytopenia results from one or more of three processes: (1) decreased bone marrow production; (2) sequestration, usually in an enlarged spleen; and/or (3) increased platelet destruction.

(58)

THROMBOCYTOSIS

Thrombocytosis is almost always due to (1) iron deficiency; (2) inflammation, cancer, or infection (reactive thrombocytosis); or (3) an underlying myeloproliferative process [essential thrombocythemia or polycythemia vera or, rarely, the 5q-myelodysplastic process

(59)

Cells Level Terminology Example

Eosinofil UP Eosinophilia Parasitic infection Netrofil Down Netropenia

(AGRANULOCYTOSIS)

typhoid fever UP NEUTROPHILIC

LEUKOCYTOSIS

Bacterial infections

Limfosit UP Lymphocytosis viral infections, malignancies

down Lymphopenia complication of corticosteroid therapy immunodeficiency states

Monosit UP Monocytosis TBC

down Monocytopenia infeksi akut, stres, dan setelah pengobatan dengan glukokortikoid

Agranucytosis

Trombosit UP thrombosytosis (1) kekurangan zat besi, (2) peradangan, kanker, atau infeksi (trombositosis reaktif) down thrombocytopenia DHF

RBC UP Erythrocytosis Hct ↑ down anemia >>>>> ALL down Pancytopenia = Aplastic

(60)

• MCV : mean cell volume, is a measure of the average red blood cell volume

• MCH : mean cell hemoglobin, is the average mass of hemoglobin per red blood cell in a sample of blood • MCHC : mean corpuscular hemoglobin

concentration, a measure of the concentration of

hemoglobin in a given volume of packed red blood cells

• RDW : red blood cell distribution width. measure of the variation of red blood cell (RBC) volume

(61)

(62)

PENDAHULUAN

SEL-SEL

(63)

HEMATOPOIESIS

= proses sintesa sel2 darah

Terdiri dari proliferasi dan differensiasi sel2 induk hematopoiesis

Tahap :

Sel induk pluripotensial  Sel induk (stem cell)  sel progenitor (CFU)  sel prekursor (blast)  sel

(64)

Sel Induk Hematoipoiesis pluripotensial • derivat mesoderm, undifferentiated • Bersifat mitosis aktif

• Bersifat pluripotent

• dapat membelah berulang, & selanjutnya differensiasi menjadi sel2 darah matur

(65)

• Berproliferasi, membentuk 2 jalur diferensiasi (2 stem cell):

* Jalur Myeloid  RBC, granulosit, monosit, Platelet ~ erythropoiesis

~ granulopiesis

~ monopiesis

~ thrombopiesis

(66)

Colony forming cell: (~ sel progenitor)

- = sel pembentuk koloni

- sebagai pembentuk koloni2 tipe2 sel darah tertentu - differensiasi menjadi sel induk unipoten ( ex : ECFC

(67)

(68)

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